1H NMR spectroscopy studies of Huntington's disease -: Correlations with CAG repeat numbers
1H NMR spectroscopy studies of Huntington's disease -: Correlations with CAG repeat numbers
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DOI：
10.1212/wnl.50.5.1357
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发表时间：
1998-05-01
期刊：
影响因子：
9.9
通讯作者：
Koroshetz, WJ
中科院分区：
文献类型：
--
作者：
Jenkins, BG;Rosas, HD;Koroshetz, WJ
亨廷顿舞蹈症 (HD) 是 4 号染色体上的基因重复扩增 (CAG) 的结果。基因缺陷的后果可能是能量代谢的进行性损害。我们之前使用局部 H-1 光谱显示 HD 中枕叶皮质乳酸增加。我们现在扩展了这些研究，结果显示，与 17 名正常对照受试者相比，31 名 KD 患者的枕叶皮质乳酸几乎升高了三倍 (p < 10(-11))。三名症状前基因阳性患者的光谱与皮质区域的正常对照受试者相同，但八分之三的人纹状体中乳酸含量升高。与最近报道的优势半球纹状体的任务相关激活增加类似，我们发现 HD 患者的纹状体乳酸水平明显不对称（左侧较高）。神经元变性的标志物、N-乙酰天冬氨酸（NAA）/肌酸减少和胆碱/肌酸水平增加是对称的。纹状体中 NAA 的减少和乳酸的增加均与症状持续时间显着相关。当除以年龄时，发现个体的纹状体 NAA 损失和乳酸增加与受试者的 CAG 重复次数直接相关，相关系数分别为 0.8 和 0.7。死后细胞损失和年龄与 CAG 重复长度之间也存在类似的相关性。总之，这些数据为 HD 中神经元激活和能量代谢缺陷之间的相互作用提供了进一步的证据，这种相互作用可能会延伸到症状前的受试者。
Huntington's disease (HD) is the result of an expanded (CAG) repeat in a gene on chromosome 4. A consequence of the gene defect may be progressive impairment of energy metabolism. We previously showed increased occipital cortex lactate in HD using localized H-1 spectroscopy. We have now extended these studies to show an almost threefold elevation in occipital cortex lactate in 31 KD patients as compared with 17 normal control subjects (p < 10(-11)). The spectra in three presymptomatic gene-positive patients were identical to normal control subjects in cortical regions, but three in eight showed elevated lactate in the striatum. Similar to recently reported increases in task-related activation of the striatum in the dominant hemisphere, we found that striatal lactate levels in HD patients were markedly asymmetric (higher on the left side). Markers of neuronal degeneration, decreased N-acetylaspartate (NAA)/creatine and increased choline/creatine levels, were symmetric. Both decreased NAA and increased lactate in the striatum significantly correlated with duration of symptoms. When divided by his or her age, an individual's striatal NAA loss and lactate increase were found to directly correlate with the subject's CAG repeat number, with correlation coefficients of 0.8 and 0.7, respectively. Similar correlations were noted between postmortem cell loss and age versus CAG repeat length. Together, these data provide further evidence for an interaction between neuronal activation and a defect in energy metabolism in HD that may extend to presymptomatic subjects.